The Phox Homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation

Recent studies have shown that phox homology (PX) domains act as phosphoinositide-binding motifs. The majority of PX domains studied show binding to phosphatidylinositol 3-monophosphate (Ptdlns(3)P), an association that allows the host protein to localize to membranes of the endocytic pathway. One issue, however, is whether PX domains may have alternative phosphoinositide binding specificities that could target their host protein to distinct subcellular compartments or allow their allosteric regulation by phosphoinositides other than PtdIns(3)P. It has been reported that the PX domain of sorting nexin 1 (SNX1) specifically binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3) (Zhong, Q., Lazar, C. S., Tronchere, H., Sato, T., Meerloo, T., Yeo, M., Songyang, Z., Emr, S. D., and Gill, G. N. (2002) Proc. Natl. Acad. Sci. U. S. A. 99,6767-6772). In the present study, we have shown that whereas SNX1 binds PtdIns(3,4,5)P-3 in protein:lipid overlay assays, in liposomes-based assays, binding is observed to PtdIns(3)P and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P-2) but not to PtdIns(3,4,5)P-3. To address the significance of PtdIns(3,4,5)P-3 binding, we examined the subcellular localization of SNX1 under conditions in which plasma membrane PtdIns(3,4,5)P-3 levels were significantly elevated. Under these conditions, we failed to observe association of SNX1 with this membrane. However, consistent with the binding to PtdIns(3)P and PtdIns(3,5)P-2 being of more physiological significance was the observation that the association of SNX1 with an early endosomal compartment was dependent on a 3-phosphoinositide-binding PX domain and the presence of PtdIns(3)P on this compartment. Finally, we somal association of SNX1 is important for its ability to regulate the targeting of internalized epidermal growth factor receptor for lysosomal degradation.

A review of guidelines and standards for telemedicine

We conducted a review to establish the range and scope of current telemedicine guidelines and standards. Published guidelines were identified by searching the Medline and Telemedicine Information Exchange (TIE) databases, and by performing a Google search using the term 'telemedicine guidelines'. Three types of guidelines were identified, namely clinical, operational and technical. Clinical guidelines included those for teleradiology, telepsychiatry, home telenursing, minor injuries telemedicine, surgical telemedicine, teledermatology and telepathology. Operational guidelines included those for email communication, Internet access and videoconferencing. Technical guidelines included those from the American Telemedicine Association and the US Office for the Advancement of Telehealth. The main standards relevant to telemedicine include those of the International Telecommunication Union and the DICOM standard. The scarcity of guidelines and standards suggests that telemedicine is not yet near to routine use. If an international telemedicine organization were to take responsibility for defining guidelines, under the direction of clinicians with appropriate telemedicine experience, this might speed up their development.

Conserved modularity and potential for alternate splicing in mouse and human Slit genes

The vertebrate Slit gene family currently consists of three members;Slit1,Slit2 and Slit3. Each gene encodes a protein containing multiple epidermal growth factor and leucine rich repeat motifs, which are likely to have importance in cell-cell interactions. In this study, we sought to fully define and characterise the vertebrate Slit gene family. Using long distance PCR coupled with in silico mapping, we determined the genomic structure of all three Slit genes in mouse and man. Analysis of EST and genomic databases revealed no evidence of further Slit family members in either organism. All three Slit genes were encoded by 36 (Slit3) or 37 (Slit1 and Slit2) exons covering at least 143 kb or 183 kb of mouse or human genomic DNA respectively. Two additional potential leucine-rich repeat encoding exons were identified within intron 12 of Slit2. These could be inserted in frame, suggesting that alternate splicing may occur in Slit2 A search for STS sequences within human Slit3 anchored this gene to D5S2075 at the 5' end (exon 4) and SGC32449 within the 3' UTR, suggesting that Slit3 may cover greater than 693 kb. The genomic structure of all Slit genes demonstrated considerable modularity in the placement of exon-intron boundaries such that individual leucine-rich repeat motifs were encoded by individual 72 by exons. This further implies the potential generation of multiple Slit protein isoforms varying in their number of repeat units. cDNA library screening and EST database searching verified that such alternate splicing does occur.

Selective entrainment of sediment graded by size and density under waves

The influence of near-bed sorting processes on heavy mineral content in suspension is discussed. Sediment concentrations above a rippled bed of mixed quartz and heavy mineral sand were measured under regular nonbreaking waves in the laboratory. Using the traditional gradient diffusion process, settling velocity would be expected to strongly affect sediment distribution. This was not observed during present trials. In fact, the vertical gradients of time-averaged suspension concentrations were found to be similar for the light and heavy minerals, despite their different settling velocities. This behavior implies a convective rather than diffusive distribution mechanism. Between the nonmoving bed and the lowest suspension sampling point, fight and heavy mineral concentration differs by two orders of magnitude. This discrimination against the heavy minerals in the pickup process is due largely to selective entrainment at the ripple face. Bed-form dynamics and the nature of quartz suspension profiles are found to be little affected by the trialed proportion of overall heavy minerals in the bed (3.8-22.1%).